1#------------------------------------------------------------------------------ 2# woman.model 3# A PK model for woman, based on Luecke et al. 1994 4# 5# May 2002 - Sandrine Micallef - various modifications for 6# correction of Luecke's model,about human life gestation. 7# Jul 2002 - Frederic Bois - various corrections 8# Sep 2002 - Sandrine Micallef - checking against ICRP ref parameter values 9# Dec 2002 - Frederic Bois - introduction of renal elimination, inhalation 10# input, and rewriting of several comments. Changing the fetal weights 11# to kg for consistency, and the list of ouputs. Correction of the 12# fetal liver weight parameters and biliary output for mother and fetus. 13# Reintroduction of placental metabolism. Introduction of gut and lung 14# metabolism for the mother. Modification of gestational age. Modifications 15# to allow simulation before pregnancy. Introduction of several variables 16# for mass balance checking. Correction of fetal blood concentrations. 17# Nov 2003 - Frederic Bois added life time evolution of the mother and 18# multiple pregnancies. 19# Feb 2005 - El Hadji Kone - deletion of the gestation. 20# Mar 2005 - F. Bois: introduction of a null output (set at zero) 21# 22# Units: 23# Volumes: L 24# Time: min 25# Flows: L/min 26# Concentrations: mM (ie mmol/L) 27# Vmax: mM/min 28# Km: mM 29# Masses: kg 30# Height: m 31# Perfusion rates: L/min/kg of tissue 32# 33# Copyright (c) 1993-2008 Free Software Foundation, Inc. 34# 35#------------------------------------------------------------------------------ 36 37States = {Q_adip, # Quantity of chemical in body adipose (mmol) 38 Q_adrenal, # ... in adrenal (mmol) 39 Q_art, # ... in arterial blood (mmol) 40 Q_brain, # ... in brain (mmol) 41 Q_breast, # ... in breast(mmol) 42 Q_gut, # ... in gut (mmol) 43 Q_gut_lumen, # ... in gut lumen (mmol) 44 Q_heart, # ... in heart (mmol) 45 Q_kidney, # ... in kidney (mmol) 46 Q_liver, # ... in liver (mmol) 47 Q_lung, # ... in lung (mmol) 48 Q_marrow, # ... in bone marrow + perf bone (mmol) 49 Q_muscle, # ... in muscle (mmol) 50 Q_other, # ... in other (mmol) 51 Q_pancreas, # ... in pancreas (mmol) 52 Q_skin, # ... in skin (mmol) 53 Q_spleen, # ... in spleen (mmol) 54 Q_stomach, # ... in stomach (mmol) 55 Q_stom_lumen, # ... in stomach lumen (mmol) 56 Q_thyroid, # ... in thyroid (mmol) 57 Q_uterus, # ... in uterus (mmol) 58 Q_ven, # ... in venous blood (mmol) 59 Q_met_liver, # ... metabolized in liver (mmol) 60 Q_met_lung, # ... metabolized in lung (mmol) 61 Q_met_gut, # ... metabolized in gut (mmol) 62 Q_ing, # ... ingested by the woman (mmol) 63 Q_inh, # ... inhaled by the woman (mmol) 64 Q_exhaled, # ... exhaled by the woman (mmol) 65 Q_feces, # ... fecally excreted by the woman (mmol) 66 Q_urine}; # ... renally excreted by the woman (mmol) 67 68 69Outputs = {C_exh, # Concentration of chemical in exhaled air (mM) 70 C_adip, # ... in adipose (mM) 71 C_adrenal, # ... in adrenal (mM) 72 C_art, # ... in arterial blood (mM) 73 C_brain, # ... in brain (mM) 74 C_breast, # ... in breast(mM) 75 C_gut, # ... in gut (mM) 76 C_gut_lumen, # ... in gut lumen (mM) 77 C_heart, # ... in heart (mM) 78 C_kidney, # ... in kidney (mM) 79 C_liver, # ... in liver (mM) 80 C_lung, # ... in lung (mM) 81 C_marrow, # ... in bone marrow (mM) 82 C_muscle, # ... in muscle (mM) 83 C_other, # ... in other (mM) 84 C_pancreas, # ... in pancreas (mM) 85 C_skin, # ... in skin (mM) 86 C_spleen, # ... in spleen (mM) 87 C_stomach, # ... in stomach (mM) 88 C_stom_lumen, # ... in stomach lumen (mM) 89 C_thyroid, # ... in venous thyroid (mM) 90 C_uterus, # ... in uterus (mM) 91 C_ven, # ... in venous blood (mM) 92 C_null, # Null output, e.g. bone or gas (set to zero) 93 94 Q_total}; # Total quantity in body and excreted (mmol) 95 96Inputs = {C_inh, # Concentration inhaled (mM) 97 Q_ing_rate}; # Ingestion rate (mmol/min) 98 99 100 101# Nominal parameter values 102# ======================== 103 104# Physiological and pharmacokinetic parameters 105# -------------------------------------------- 106 107# Fraction of dead space in lung 108F_dead_space = 0.67; 109 110# Age in years 111Age = 30; 112 113# Fraction of arterial blood 114# Calculated from Filser 2000 p.43 115Fr_art_blood = 0.0178 / (0.0178 + 0.0533); 116 117# Tissue volumic weight are assumed to be equal to 1 118# excepted for adipose tissue (cf Brown et al. 97 p.433) 119density_adip = 0.9; 120density_bone = 2.0; 121 122# Scaling factors for the volume of the organs 123# Unit = L/meter of height 124# sc_V_ have been calculated for a standard woman : 1.63m 63kg 125# and using the organ weights given by the ICRP. 2001 126# density for the organs is supposed equal to 1 excepted for 127# adipose tissues (0.9) and bones (2) 128 129sc_V_adrenal = 8.0E-3; 130sc_V_bone = 1.564; 131sc_V_brain = 0.798; 132sc_V_gut = 0.589; 133sc_V_gut_lumen = 0.331; 134sc_V_heart = 0.153; 135sc_V_kidney = 0.169; 136sc_V_liver = 0.859; 137sc_V_lung = 0.215; 138sc_V_marrow = 1.656; # yellow + red 139sc_V_muscle = 11.043; 140sc_V_other = 4.012; 141sc_V_pancreas = 0.052; 142sc_V_skin = 1.530; 143sc_V_spleen = 0.092; 144sc_V_stomach = 0.086; 145sc_V_stom_lumen= 0.098; 146sc_V_thyroid = 0.010; 147sc_V_uterus = 0.049; 148 149 150# Perfusion per unit mass of organ. 151# These have been calculated as follows: 152# sc_F_organ = %blood_flow_rate * Card_output / organ_weight 153# the values have been taken from ICRP 2001 154# Organ weight : Table R8 p2-5, 155# Cardiac output : Table R26 p2-23 156# Blood_flow : Table R15 & R17 p7-11 or William & Leggett 157# Table R31 p2-26 for perfusion of breast and uterus assuming 158# a factor 10 growth of uterus mass during pregnancy 159# Unit: L/min/kg of tissue 160 161sc_F_adip = 0.03; 162sc_F_adrenal = 1.68; 163sc_F_brain = 0.49; 164sc_F_breast = 0.27; 165sc_F_eport = 0.25; 166sc_F_gut = 0.95; 167sc_F_heart = 1.08; 168sc_F_kidney = 4.41; 169sc_F_marrow = 0.10; 170sc_F_muscle = 0.04; 171sc_F_pancreas= 0.60; 172sc_F_skin = 0.29; 173sc_F_spleen = 1.07; 174sc_F_stomach = 0.52; 175sc_F_thyroid = 4.72; 176sc_F_uterus = 1.095; 177sc_F_other = 0.027; 178 179 180# Transits; Unit: L/min 181Fl_stom_lumen = 0.208 / 60.0; # Intestinal transit for stomach -> gut 182 # ICRP R8 and R23 p. 6-15 183Fl_gut_lumen = 0.005 / 60.0; # Intestinal transit for gut (feces) 184 # ICRP R8 and R23 p. 6-15 185 186 187 188# Parameters indicating the fraction of fat in each organ 189# comming from Fiserova-Bergerova 1983 190# or references found in Van der Mollen 1996 191frac_fat_blood = 0.0052; # Papke et al 89. 192 193frac_fat_adip = 0.859; # Beck 90, Duarte-Davidson 93, Patterson 86 194 # Ryan 86 Ryan 85b Schecter 85 195 # refs in Van der Molen 96 196frac_fat_adrenal = 0.049; # Default value corresponding to 197 # "Remaining organs de Van der Molen" 198frac_fat_brain = 0.11; # Fiserova-Bergerova 1983 199frac_fat_breast = 0.049; # Default value 200frac_fat_gut = 0.065; # Fiserova-Bergerova 1983 201frac_fat_gut_lumen = 0.049; # Default value 202frac_fat_heart = 0.083; # Fiserova-Bergerova 1983 203frac_fat_kidney = 0.052; # Fiserova-Bergerova 1983 204frac_fat_liver = 0.049; # Lenter 81, ref in Van der Molen 96 205frac_fat_lung = 0.017; # Fiserova-Bergerova 1983 206frac_fat_marrow = 0.186; # Clarys & Martin 85,ref in Van der Molen 96 207frac_fat_muscle = 0.064; # Lenter 81 & Ryan 85, 208 # ref in Van der Molen 96 209frac_fat_other = 0.049; # Default value 210frac_fat_pancreas = 0.105; # Fiserova-Bergerova 1983 211frac_fat_skin = 0.150; # Fiserova-Bergerova 1983 212frac_fat_spleen = 0.030; # Fiserova-Bergerova 1983 213frac_fat_stomach = 0.049; # Default value 214frac_fat_stom_lumen = 0.049; # Default value 215frac_fat_thymus = 0.049; # Default value 216frac_fat_thyroid = 0.049; # Default value 217frac_fat_uterus = 0.049; # Default value 218 219 220# Parameters specific of the chemical studied 221# ------------------------------------------- 222 223# Transferts depending on the agent; Unit: L/min 224Ka_stomach = 0.1; # Absorption rate constant for stomach 225Ka_gut = 0.1; # Absorption rate constant for gut 226Ke_bile = 0.0; # Biliary excretion rate constant for the woman 227 228# Lung/air PC 229PC_lung_over_air = 1; 230 231# Adipose tissue over blood partition coefficent 232PC_adip = 1; 233 234# renal elimination flow rate (L/min) 235Ke_renal = 1E-3; 236 237# hepatic metabolic rate constant scaling factor ((kg^0.25)/min) 238# Scaling to the 0.25 is supported by Hattis et al. and used by Gentry et al. 239scKm_liver = 0; 240 241# gut metabolic rate constant scaling factor ((kg^0.25)/min) 242scKm_gut = 0; 243 244# lung metabolic rate constant scaling factor ((kg^0.25)/min) 245scKm_lung = 0; 246 247 248# Other parameters that will be computed in Initialize 249 250PC_fat; 251PC_adrenal; 252PC_brain; 253PC_breast; 254PC_gut; 255PC_heart; 256PC_kidney; 257PC_liver; 258PC_lung; 259PC_marrow; 260PC_muscle; 261PC_other; 262PC_pancreas; 263PC_skin; 264PC_spleen; 265PC_stomach; 266PC_thymus; 267PC_thyroid; 268PC_uterus; 269 270# Parameters changing with time. 271height; 272dtmp; 273Km_liver; 274Km_gut; 275Km_lung; 276 277W_lean; 278W_total; # Total weight of the woman, bone 279V_blood; 280V_adip; 281V_adrenal; 282V_art; 283V_ven; 284V_bone; 285V_brain; 286V_breast; 287V_gut; 288V_gut_lumen; 289V_heart; 290V_kidney; 291V_liver; 292V_lung; 293V_marrow; 294V_muscle; 295V_other; 296V_pancreas; 297V_skin; 298V_spleen; 299V_stomach; 300V_stom_lumen; 301V_thyroid; 302V_uterus; 303 304F_adip; 305F_adrenal; 306F_alv; 307F_brain; 308F_breast; 309F_eport; 310F_gut; 311F_heart; 312F_kidney; 313F_marrow; 314F_muscle; 315F_other; 316F_pancreas; 317F_pul; 318F_skin; 319F_spleen; 320F_stomach; 321F_thyroid; 322F_uterus; 323F_liver; 324F_blood; 325 326Initialize { 327 328 329 # Pure fat /blood partition coef. 330 331 PC_fat = PC_adip / frac_fat_adip; 332 333 # Tissue over blood partition coefficients 334 335 PC_adrenal = frac_fat_adrenal * PC_fat; 336 PC_brain = frac_fat_brain * PC_fat; 337 PC_breast = frac_fat_breast * PC_fat; 338 PC_gut = frac_fat_gut * PC_fat; 339 PC_heart = frac_fat_heart * PC_fat; 340 PC_kidney = frac_fat_kidney * PC_fat; 341 PC_liver = frac_fat_liver * PC_fat; 342 PC_lung = frac_fat_lung * PC_fat; 343 PC_marrow = frac_fat_marrow * PC_fat; 344 PC_muscle = frac_fat_muscle * PC_fat; 345 PC_other = frac_fat_other * PC_fat; 346 PC_pancreas = frac_fat_pancreas * PC_fat; 347 PC_skin = frac_fat_skin * PC_fat; 348 PC_spleen = frac_fat_spleen * PC_fat; 349 PC_stomach = frac_fat_stomach * PC_fat; 350 PC_thymus = frac_fat_thymus * PC_fat; 351 PC_thyroid = frac_fat_thyroid * PC_fat; 352 PC_uterus = frac_fat_uterus * PC_fat; 353 354 # tissue volumes (L) are supposed to be proportionnal to the 355 # Woman height, excepted for the adipose tissue 356 357 height = (Age < 1 ? 51 + Age * (76-51) : 358 (Age < 5 ? 76 + (Age-1) * (109-76) / 4.0 : 359 (Age < 10 ? 109 + (Age-5) * (138-109) / 5.0 : 360 (Age < 15 ? 138 + (Age-10) * (161-138) / 5.0 : 361 (Age < 20 ? 161 + (Age-15) * (163-161) / 5.0 : 362 163))))) * 0.01; 363 364 V_adrenal = sc_V_adrenal * height; 365 V_bone = sc_V_bone * height; 366 V_brain = sc_V_brain * height; 367 V_gut = sc_V_gut * height; 368 V_gut_lumen = sc_V_gut_lumen * height; 369 V_heart = sc_V_heart * height; 370 V_kidney = sc_V_kidney * height; 371 V_liver = sc_V_liver * height; 372 V_lung = sc_V_lung * height; 373 V_marrow = sc_V_marrow * height; 374 V_muscle = sc_V_muscle * height; 375 V_other = sc_V_other * height; 376 V_pancreas = sc_V_pancreas * height; 377 V_skin = sc_V_skin * height; 378 V_spleen = sc_V_spleen * height; 379 V_stomach = sc_V_stomach * height; 380 V_stom_lumen = sc_V_stom_lumen* height; 381 V_thyroid = sc_V_thyroid * height; 382 383 384 385 # Volumes of the organs changing with the time, 386 # computed with the equations from Luecke 94 and from ICRP data and Van 387 # Molen model after age 14 388 389 V_adip = (Age < 1 ? 0.37 + Age * (2.3-0.37) : 390 (Age < 5 ? 2.3 + (Age-1) * (3.6-2.3) / 4.0 : 391 (Age < 10 ? 3.6 + (Age-5) * (6-3.6) / 5.0 : 392 (Age < 15 ? 6.0 + (Age-10) * (14-6) / 5.0 : 393 14 + (Age-15) * 17 / 55.0)))) / density_adip; 394 395 V_blood = (Age < 1 ? 0.27 + Age * (0.5-0.27) : 396 (Age < 5 ? 0.5 + (Age-1) * (1.4-0.5) / 4.0 : 397 (Age < 10 ? 1.4 + (Age-5) * (2.4-1.4) / 5.0 : 398 (Age < 15 ? 2.4 + (Age-10) * (3.3-2.4) / 5.0 : 399 (Age < 20 ? 3.3 + (Age-15) * (3.9-3.3) / 5.0 : 400 3.9))))); 401 402 V_art = V_blood * Fr_art_blood; 403 V_ven = V_blood - V_art; 404 405 V_breast = (Age < 10 ? 0.01 : 406 (Age < 15 ? 0.01 + (Age-10) * (0.25-0.01) / 5.0 : 407 (Age < 20 ? 0.25 + (Age-15) * (0.5-0.25) / 5.0 : 0.5))); 408 409 V_uterus = sc_V_uterus * height; 410 411 W_lean = V_adrenal + V_blood + 412 V_bone * density_bone + V_brain + V_breast + 413 V_gut + V_gut_lumen + V_heart + V_kidney + 414 V_liver + V_lung + V_marrow + V_muscle + 415 V_other + V_pancreas + V_skin + V_spleen + 416 V_stomach + V_stom_lumen + V_thyroid + V_uterus; 417 418 W_total = W_lean + V_adip * density_adip; 419 420 # Scale metabolism to body masses 421 422 dtmp = pow(W_lean, 0.25); 423 Km_liver = scKm_liver / dtmp; 424 Km_gut = scKm_gut / dtmp; 425 Km_lung = scKm_lung / dtmp; 426 427 # Compute actual blood flows 428 # Unit: L/min 429 430 F_adip = sc_F_adip * V_adip; 431 F_adrenal = sc_F_adrenal * V_adrenal; 432 F_brain = sc_F_brain * V_brain; 433 F_breast = sc_F_breast * V_breast; 434 F_eport = sc_F_eport * V_liver; 435 F_gut = sc_F_gut * V_gut; 436 F_heart = sc_F_heart * V_heart; 437 F_kidney = sc_F_kidney * V_kidney; 438 F_marrow = sc_F_marrow * V_marrow; 439 F_muscle = sc_F_muscle * V_muscle; 440 F_other = sc_F_other * V_other ; 441 F_pancreas = sc_F_pancreas * V_pancreas; 442 F_skin = sc_F_skin * V_skin; 443 F_spleen = sc_F_spleen * V_spleen; 444 F_stomach = sc_F_stomach * V_stomach; 445 F_thyroid = sc_F_thyroid * V_thyroid; 446 F_uterus = sc_F_uterus * V_uterus; 447 448 F_liver = F_eport + F_spleen + F_pancreas + F_gut + F_stomach; 449 450 F_blood = F_adip + F_adrenal + F_brain + F_breast + 451 F_heart + F_kidney + F_liver + F_marrow + F_muscle + 452 F_other + F_skin + F_thyroid + F_uterus; 453 454 455 456 # Note: lung is irrigated by a bifurcation and does not enter in the 457 # formula above. 458 # Pulmonary Flow rate (L/min) (ref ICRP Pub 89, p 99). 459 460 F_pul = (Age < 1 ? 1.5 + Age * (3.7-1.5) : 461 (Age < 5 ? 3.7 + (Age-1) * (5.3-3.7) / 4.0 : 462 (Age < 10 ? 5.3 + (Age-5) * (6.3-5.3) / 5.0 : 463 (Age < 15 ? 6.3 + (Age-10) * (6.7-6.3) / 5.0 : 464 (Age < 20 ? 6.7 + (Age-15) * (6.5-6.7) / 5.0 : 465 6.7))))); 466 467 # Alveolar flow rate 468 F_alv = F_pul * F_dead_space; 469 470} # End of initialize 471 472 473Dynamics { 474 475 # Concentrations in venous blood at the organ exit and in tissues 476 477 C_adip = Q_adip / V_adip; 478 C_adip_v = C_adip / PC_adip; 479 480 C_adrenal = Q_adrenal / V_adrenal; 481 C_adrenal_v = C_adrenal / PC_adrenal; 482 483 C_brain = Q_brain / V_brain; 484 C_brain_v = C_brain / PC_brain; 485 486 C_breast = Q_breast / V_breast; 487 C_breast_v = C_breast / PC_breast; 488 489 C_gut = Q_gut / V_gut; 490 C_gut_v = C_gut / PC_gut; 491 492 C_heart = Q_heart / V_heart; 493 C_heart_v = C_heart / PC_heart; 494 495 C_kidney = Q_kidney / V_kidney; 496 C_kidney_v = C_kidney / PC_kidney; 497 498 C_liver = Q_liver / V_liver; 499 C_liver_v = C_liver / PC_liver; 500 501 C_lung = Q_lung / V_lung; 502 C_lung_v = C_lung / PC_lung; 503 504 C_marrow = Q_marrow / V_marrow; 505 C_marrow_v = C_marrow / PC_marrow; 506 507 C_muscle = Q_muscle / V_muscle; 508 C_muscle_v = C_muscle / PC_muscle; 509 510 C_other = Q_other / V_other; 511 C_other_v = C_other / PC_other; 512 513 C_pancreas = Q_pancreas / V_pancreas; 514 C_pancreas_v = C_pancreas / PC_pancreas; 515 516 C_skin = Q_skin / V_skin; 517 C_skin_v = C_skin / PC_skin; 518 519 C_spleen = Q_spleen / V_spleen; 520 C_spleen_v = C_spleen / PC_spleen; 521 522 C_stomach = Q_stomach / V_stomach; 523 C_stomach_v = C_stomach / PC_stomach; 524 525 C_thyroid = Q_thyroid / V_thyroid; 526 C_thyroid_v = C_thyroid / PC_thyroid; 527 528 C_uterus = Q_uterus / V_uterus; 529 C_uterus_v = C_uterus / PC_uterus; 530 531 532 533 534 535 # other compartment concentrations for which PC_ is not needed 536 # because equal to 1 (PC_ven and PC_art) or because 537 # they are not directly irrigated by blood (diffusion) 538 539 C_gut_lumen = Q_gut_lumen / V_gut_lumen; 540 C_stom_lumen = Q_stom_lumen / V_stom_lumen; 541 C_art = Q_art / V_art; 542 C_ven = Q_ven / V_ven; 543 544 545 # Differentials 546 547 dt(Q_ing) = Q_ing_rate; 548 549 dt(Q_stom_lumen) = Q_ing_rate - 550 (Fl_stom_lumen + Ka_stomach) * C_stom_lumen; 551 552 dt(Q_stomach ) = Ka_stomach * C_stom_lumen + 553 F_stomach * (C_art - C_stomach_v); 554 555 dt(Q_feces) = Fl_gut_lumen * C_gut_lumen; 556 557 dt(Q_gut_lumen) = Fl_stom_lumen * C_stom_lumen + Ke_bile * C_liver - 558 Ka_gut * C_gut_lumen - dt(Q_feces); 559 560 dt(Q_met_gut) = Km_gut * Q_gut; 561 562 dt(Q_gut) = Ka_gut * C_gut_lumen + 563 F_gut * (C_art - C_gut_v) - dt(Q_met_gut); 564 565 dt(Q_met_liver) = Km_liver * Q_liver; 566 567 dt(Q_liver) = F_eport * C_art + F_spleen * C_spleen_v + 568 F_pancreas * C_pancreas_v + F_gut * C_gut_v + 569 F_stomach * C_stomach_v - F_liver * C_liver_v - 570 Ke_bile * C_liver - dt(Q_met_liver); 571 572 dt(Q_adip) = F_adip * (C_art - C_adip_v); 573 dt(Q_adrenal) = F_adrenal * (C_art - C_adrenal_v); 574 dt(Q_brain) = F_brain * (C_art - C_brain_v); 575 dt(Q_breast) = F_breast * (C_art - C_breast_v); 576 dt(Q_heart) = F_heart * (C_art - C_heart_v); 577 578 dt(Q_inh) = F_alv * C_inh; 579 580 dt(Q_exhaled) = F_alv * (C_lung / PC_lung_over_air); 581 582 dt(Q_met_lung) = Km_lung * Q_lung; 583 584 dt(Q_lung) = F_blood * (C_ven - C_lung_v) + dt(Q_inh) - 585 dt(Q_exhaled) - dt(Q_met_lung); 586 587 dt(Q_urine) = Ke_renal * C_kidney; 588 589 dt(Q_kidney) = F_kidney * (C_art - C_kidney_v) - dt(Q_urine); 590 591 dt(Q_marrow) = F_marrow * (C_art - C_marrow_v); 592 dt(Q_muscle) = F_muscle * (C_art - C_muscle_v); 593 dt(Q_other) = F_other * (C_art - C_other_v); 594 dt(Q_pancreas) = F_pancreas * (C_art - C_pancreas_v); 595 dt(Q_skin) = F_skin * (C_art - C_skin_v); 596 dt(Q_spleen) = F_spleen * (C_art - C_spleen_v); 597 dt(Q_thyroid) = F_thyroid * (C_art - C_thyroid_v); 598 599 dt(Q_art) = F_blood * (C_lung_v - C_art); 600 601 dt(Q_ven) = C_skin_v * F_skin + C_heart_v * F_heart + 602 C_other_v * F_other + C_liver_v * F_liver + 603 C_adip_v * F_adip + C_adrenal_v * F_adrenal + 604 C_marrow_v * F_marrow + C_breast_v * F_breast + 605 C_muscle_v * F_muscle + C_brain_v * F_brain + 606 C_thyroid_v * F_thyroid + C_uterus_v * F_uterus + 607 C_kidney_v * F_kidney - F_blood * C_ven; 608 609 dt(Q_uterus) = F_uterus * (C_art - C_uterus_v); 610 611 # Mass balance check 612 613 Q_total = Q_adip + Q_adrenal + Q_art + Q_brain + Q_breast + Q_gut + 614 Q_gut_lumen + Q_heart + Q_kidney + Q_liver + Q_lung + 615 Q_marrow + Q_muscle + Q_other + Q_pancreas + Q_skin + 616 Q_spleen + Q_stomach + Q_stom_lumen + Q_thyroid + Q_uterus + 617 Q_ven + Q_met_liver + Q_met_lung + Q_met_gut + Q_exhaled + 618 Q_feces + Q_urine; 619 620} # End of Dynamics 621 622 623CalcOutputs { 624 625 # Exhaled air concentration (mM) 626 C_exh = 0.7 * C_ven + 0.3 * C_inh; 627 628 C_null = 0; 629 630} # End of CalcOutputs 631 632End. 633